Metabolomic changes in murine serum following inhalation exposure to gasoline and diesel engine emissions

Abstract

The adverse health effects of environmental exposure to gaseous and particulate components of vehicular emissions are a major concern among urban populations. A link has been established between respiratory exposure to vehicular emissions and the development of cardiovascular disease (CVD), but the mechanisms driving this interaction remain unknown. Chronic inhalation exposure to mixed vehicle emissions has been linked to CVD in animal models. This study evaluated the temporal effects of acute exposure to mixed vehicle emissions (MVE; mixed gasoline and diesel emissions) on potentially active metabolites in the serum of exposed mice. C57Bl/6 mice were exposed to a single 6 hour exposure to filtered air (FA) or MVE (100 or 300 µg/m3) by whole body inhalation. Immediately after and 18 hours after the end of the exposure period, animals were sacrificed for serum and tissue collection. Serum was analyzed for metabolites that were differentially present between treatment groups and time points. Changes in metabolite levels suggestive of increased oxidative stress (oxidized glutathione, cysteine disulfide, taurine), lipid peroxidation (13-HODE, 9-HODE), energy metabolism (lactate, glycerate, branched chain amino acid catabolites, butrylcarnitine, fatty acids), and inflammation (DiHOME, palmitoyl ethanolamide) were observed immediately after the end of exposure in the serum of animals exposed to MVE relative to those exposed to FA. By 18 hours post exposure, serum metabolite differences between animals exposed to MVE versus those exposed to FA were less pronounced. These findings highlight complex metabolomics alterations in the circulation following inhalation exposure to a common source of combustion emissions.

Air pollution and cardiovascular disease: car sick

“…159 Finally, while conventional cytokines such as TNF-a, IL-6, and CRP do not seem to fully fit the bill, there is convincing evidence for an, as-yet, unidentified blood-borne mediator that could bring together the different stages of this pathway. [160][161][162] The second theory is that inhaled pollutants activate alveolar receptors, stimulating sensory afferents that alter cardiovascular function via changes in autonomic balance or neuroendocrine regulation. 143,163,164 The pattern of HRV changes in response to PM would clearly indicate a shift in the balance of the autonomic nervous system towards reduced parasympathetic activity and increased sympathetic activity.…”

Metabolomics Profiling before, during, and after the Beijing Olympics: A Panel Study of Within-Individual Differences during Periods of High and Low Air Pollution

“…Over the past years, the use of metabolomics approaches to study environmental exposure-related biological mechanisms has increased. Previous studies using animal models have associated air pollution exposure with a small number of targeted metabolites including arachidonic acid (AA), prostaglandin normalD2 (PGD2), and hydroxyoctadecadienoic acids (Brower et al. 2016; Cruickshank-Quinn et al.…”

Multi-omics signatures of the human early life exposome

“…Indoor levels of PM2.5 absorbance, a marker of black/elemental carbon originating from combustion, were associated with methylation of 9 CpGs, including two in common with tobacco exposure (Figure S5C; Table S3) , and with decreased levels of serum branched amino acids (aka BCAA: Ile, Leu, and Val), acylcarnitine C4 (butyrylcarnitine) and two sphingolipids. There is emerging, although somewhat conflicting evidence of metabolic changes related to outdoor air pollution in humans and animals (Brower et al, 2016; Miller et al, 2015; van Veldhoven et al, 2019). Similar to our results, lower BCAA and acylcarnitines were detected in young obese participants exposed to near-roadway air pollution (Chen et al, 2019).…”